DESCRIPTION (Investigator's Abstract): The investigator requests three years of support to study the effects of gonadal steroids on expression of NGF and NGF receptors, and correlate the results with behavioral studies after steroid treatment. In preliminary work, the investigator has found that treatment of female gonadectomized rats for two weeks with estrogen results in a decrease in the number of cell bodies immunoreactive for the NGF receptor in the basal forebrain, similar to effects observed after fimbria/fornix lesions. He now proposes to extend these observations to males and to investigate estrogenic versus androgenic mechanisms by treatments with testosterone or dihydrotestosterone. The investigator notes the close relationship between NGF-R and ChAT expression in the basal forebrain and will therefore compare the time course of steroid effects on the expression of these to markers to see if they are correlated. In addition, he will determine if the effects of chronic exposure to gonadal steroids are reversible. In situ hybridization studies are also proposed to examine relative levels of NGF and NGF-R message after steroid treatment with particular attention paid to basal forebrain and hypothalamic regions. The effects o exogenous NGF on NGF-R and ChAT expression in the hypothalamus will be determined immunocytochemically to further investigate the relationship between NGF and gonadal steroids - in this case in regions where steroid-regulated sexual behaviors are more directly mediated. The final aim is devoted to behavioral testing of gonadectomized rats after long term treatment with gonadal steroids in order to assess spatial learning and memory and correlate the results with the anatomical studies. The tasks selected for this analysis have been shown to be dependent, at least in part, on basal forebrain cholinergic pathways.